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NCCN Flash Updates™: NCCN Guidelines Updated NCCN Flash Update sent March 25, 2013 NCCN has published updates for the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia (ALL). These NCCN Guidelines® are currently available as Version 1.2013. Ph-negative ALL (ALL-5 and ALL-6) For consolidation options in AYA patients and Adults (age > 65 years), factors to consider for allogeneic HSCT modified to include poor-risk cytogenetics and to remove WBC counts (except as a footnote for the latter). Relapsed/Refractory ALL (ALL-7) The treatment recommendations for AYA and Adult patients consolidated. The following footnote added for allogeneic HSCT: For patients relapsing after allogeneic HSCT, a second allogeneic HSCT and/or donor lymphocyte infusion (DLI) can be considered. Donor lymphocyte infusion (DLI) removed as a treatment option for Ph+ ALL (except as a footnote, as mentioned above). Supportive Care (ALL-B) Prophylactic anti-infectives (ALL-B 1 of 4) The following added: VZV prophylaxis (eg, acyclovir) for at least 1 year after HSCT in transplant patients; and HBV prophylaxis (eg, adefovir, entecavir, lamivudine) for at least 6-12 months after HSCT depending on HBV serology. Steroid management (ALL-B 1 of 4) The following added: Consider dose reduction for steroid-induced psychosis and mood alteration. Asparaginase Toxicity Management (ALL-B 3 of 4) Toxicity grade clarified as CTCAE. Toxicity grades changed from 2, 3, 4 to 1, 2, 3-4. Systemic allergic reaction/anaphylaxis: recommendations for dosing substitutions removed. Pancreatitis; Grade 1 and 2 recommendations combined: Continue asparaginase for asymptomatic amylase or lipase elevation >3.0 x ULN (chemical pancreatitis) or only radiologic abnormalities; observe closely for rising amylase or lipase levels. Continue pegaspargase for nonsymptomatic chemical pancreatitis but observe patient closely for development of symptomatic pancreatitis for early treatment. Grade 3 and 4 recommendations combined: Permanently discontinue all asparaginase for clinical pancreatitis (vomiting, severe abdominal pain) with amylase or lipase elevation >3 x ULN for >3 days and/or development of pancreatic pseudocyst. Asparaginase Toxicity Management (ALL-B 4 of 4) Non-CNS hemorrhage; Grade 2 to 4 recommendations combined: For bleeding in conjunction with hypofibrinogenemia, withhold asparaginase until bleeding £ grade 1, until acute toxicity and clinical signs resolve, and coagulant replacement therapy stable or completed. CNS hemorrhage; Grade 1 and 2 recommendations combined: Discontinue all asparaginase; if CNS symptoms and signs are fully resolved and significant asparaginase remains to be administered, may resume asparaginase therapy at a lower dose and/or longer intervals between doses. CNS thrombosis; Grade 2 recommendation modified with the addition of “with closely monitored anticoagulation.” Evaluation and Treatment of Extramedullary Involvement (ALL-C) CNS leukemia clarified as having CNS-3 and/or cranial nerve involvement. Principles of Chemotherapy (ALL-D) Induction regimens for Ph-positive ALL (ALL-D 1 of 4) Adult patients aged ³40 years; the following treatment option added: TKIs + vincristine + dexamethasone. Protocols for AYA patients aged 15-39 years; the following treatment options added: TKIs + hyper-CVAD: imatinib or dasatinib; and hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose methotrexate, and cytarabine. TKIs + multiagent chemotherapy: imatinib; and daunorubicin, vincristine, prednisone, and cyclophosphamide. Maintenance regimens (ALL-D 1 of 4) Modified to: Monthly vincristine/prednisone pulses (for 2-3 years). May include weekly methotrexate + daily mercaptopurine (6-MP) as tolerated. The following footnote added: May be necessary to reduce dose/eliminate antimetabolite in the setting of myelosuppression and/or hepatotoxicity. Salvage regimens for relapsed/refractory ALL (ALL-D 3 of 4) Ph-positive ALL; Ponatinib added as a treatment option. Treatment Options Based on BCR-ABL Kinase Domain Mutation Status (ALL-G) This table was updated to include Ponatinib. The Discussion section was updated to reflect all changes within the algorithm. For the complete updated versions of the NCCN Guidelines, the NCCN Drugs and Biologics Compendium (NCCN Compendium®), and the NCCN Chemotherapy Order Templates (NCCN Templates®), please visit NCCN.org. To access the NCCN Biomarkers Compendium™, please visit NCCN.org/biomarkers. To view the NCCN Guidelines for Patients®, please visit NCCN.com. Free NCCN Guidelines mobile apps for iPad and Android are now available! Visit NCCN.org/mobile/tablet.

IXL Gene in pancreatic cancer

IXL, Intersex like cell, a survival regulator, located on 19q13,
note the q location of the amplicon ( a piece of DNA or RNA that is the source and/or product of natural or artificial amplification or replication events) the 10% rate of amplification is clearly higher than the usual few, with 5% of secondary amplification making this a clear Amplicon.  Knocking down this stops cells in Go-G1 per Kuuselo et al.  As the Component of the Mediator complex, it is a co-activator that  regulates the transcription of nearly all RNA polymerase II-dependent genes which are at the origin of m-RNA formation.  It puts this gene at the initiation complex.  At the sole of enzyme fabrication, regulator fabrication, and formation of transcription factors.  Tinkering with gene blocks transcription. That's it!  Even splicing will in fact be affected to some extent.

This gene interacts with AP-1

and

AP-1 transcription factor

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AP-1/DNA complex. Crystallographic structure (PDB 1FOS) of the AP-1 heterodimer comprising c-Fos (cyan) and c-Jun (green) complexed with DNA (brown).

In the field of molecular biology, the activator protein 1 (AP-1) is a transcription factor which is a heterodimeric protein composed of proteins belonging to the c-Fos, c-Jun, ATF and JDP families. It regulates gene expression in response to a variety of stimuli, including cytokines, growth factors, stress, and bacterial and viral infections.^[1] AP-1 in turn controls a number of cellular processes including differentiation, proliferation, and apoptosis.^[2]
AP-1 upregulates transcription of genes containing the TPA DNA response element (TRE; 5'-TGAG/CTCA-3').^[1] AP-1 binds to this DNA sequence via a basic amino acid region, while the dimeric structure is formed by a leucine zipper.^[3]　

SO HERE PANCREATITIS, ALCOHOL, VIRUSES AND OTHER STRESSORS FIND THEIR WAY TO THE PATHOGENESIS OF PANCREATIC CANCERS!

It is also connected to

CUTL1

and it needs CUTL-1 now to have muscle, but unleash the powerful regulator it encloses.  It may use this regulator to silence other genes that may lead to apoptosis. The IXL gene is a strategist in its advancement of pancreatic cancer.  This is a major target!

And 3rd, and not the least 

it interferes with ATF2

'This gene encodes a transcription factor that is a member of the leucine zipper family of DNA-binding proteins. This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. The protein forms a homodimer or heterodimer with c-Jun and stimulates CRE-dependent transcription. The protein is also a histone acetyltransferase (HAT) that specifically acetylates histones H2B and H4 in vitro; thus, it may represent a class of sequence-specific factors that activate transcription by direct effects on chromatin components. Additional transcript variants have been identified but their biological validity has not been determined.^[1]
The gene atf2 is located at human chromosome 2q32.^[2] '  (wikipedia

BELIEVE ME WHEN THEY SAY LEUCINE, THE MTORs ARE NOT FAR BEHIND!!!